The present investigations have been designed to evaluate, in a longitudinal and cross-sectional study, the relative contributions of genetic, in utero and nutritional factors to the pathogenesis of childhood obesity. Oral glucose tolerance tests with measurement of serum insulin (or C. peptide) and plasma glucagon will be performed in gestational and insulin-requiring diabetics during each trimester of pregnancy. At the same time, adipose tissue cell size will be determined on needle aspirates of fat tissue. Diabetic control will be assayed via monthly hemoglobin A1C, triglyceride, cholesterol and plasma amino acid measurements. Attempts at normalizing maternal blood glucose concentrations will consist of dietary manipulation, multiple daily insulin injections, hospitalizations when indicated and specifically insulin treatment of 50% of the gestational (or Class A) mothers. Infants born to these mothers will be followed with serial adipose tissue cellularity and metabolic studies and oral glucose tolerance tests, (with measurements of glucagon, insulin and growth hormone). Growth will be monitored with bone age determinations and careful measurements of height, weight, head circumference and skinfold thickness. In vivo and in vitro insulin sensitivity will be investigated with serial insulin tolerance tests performed with gradually increasing insulin doses between .05 to .15 units per kilogram of body weight, adipocyte responses to insulin, and adipocyte and monocyte insulin receptor studies. Thyroid function will be evaluated specifically to study alterations in T3: reverse T3 ratios particularly during periods of weight gain or loss. Nutritional evaluations will be performed frequently including during periods of hospitalization on the Clinical Research Center, and together with the other data will dietate the type(s) of intervention necessary to prevent the development of significant obesity in this at-risk population. In addition, these studies will be compared with previous ones on a group of similar children now aged 7 years and followed since birth. Finally, parallel longitudinal studies will be performed in monozygotic and dizygotic twins ages 1 day through 14 years to further elucidate genetic factors in human obesity.